Eus and ercp in the same session for biliary stones: From risk stratification to treatment strategy in different clinical conditions

Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and stone extraction is the treatment of choice for choledocholithiasis, reaching a successful clearance of the common bile duct (CBD) in up to 90% of the cases. Endoscopic ultrasound (EUS) has the best diagnostic accuracy for CBD stones, its sensitivity and specificity range being 89–94% and 94–95%, respectively. Traditionally seen as two separate entities, the two worlds of EUS and ERCP have recently come together under the new discipline of bilio-pancreatic endoscopy. Nevertheless, the complexity of both EUS and ERCP led the European Society of Gastrointestinal Endoscopy to identify quality in endoscopy as a top priority in its recent EUS and ERCP curriculum recommendations. The clinical benefits of performing EUS and ERCP in the same session are several, such as benefiting from real-time information from EUS, having one single sedation for both the diagnosis and the treatment of biliary stones, reducing the risk of cholangitis/acute pancreatitis while waiting for ERCP after the EUS diagnosis, and ultimately shortening the hospital stay and costs while preserving patients’ outcomes. Potential candidates for the same session approach include patients at high risk for CBD stones, symptomatic individuals with status post-cholecystectomy, pregnant women, and those unfit for surgery. This narrative review discusses the main technical aspects and evidence from the literature about EUS and ERCP in the management of choledocholithiasis

Contrast Harmonic-Enhanced Endoscopic Ultrasound (EUS) Is the Perfect Companion of EUS-Guided Tumor Ablation

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Role of contrast harmonic-endoscopic ultrasound in pancreatic cystic lesions

none4noIncidental pancreatic cysts (PCs) are frequently encountered in the general population often in asymptomatic patients who undergo imaging tests to investigate unrelated conditions. The detection of a PC poses a significant clinical dilemma, as the differential diagnosis is quite broad ranging from benign to malignant conditions. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) has been reported to be an accurate tool in the differential diagnosis; however, its sensitivity is suboptimal and false negative results do occur. Contrast harmonic EUS (CH-EUS) was demonstrated to be a useful tool to investigate pancreatic solid lesions to differentiate between benign and malignant ones. In the setting of PCs, CH-EUS could help identify areas of malignant growth inside the cystic cavities. Several studies have reported promising results showing malignant areas in PCs as hyperenhanced lesions. Confirmation of malignancy can then be obtained by FNA, which should be precisely targeted according to the findings of the contrast harmonic study.openSerrani, Marta; Lisotti, Andrea; Caletti, Giancarlo; Fusaroli, PietroSerrani, Marta; Lisotti, Andrea; Caletti, Giancarlo; Fusaroli, Pietr

Knife-assisted resection (KAR) for small rectal neuroendocrine neoplasia

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Chronic NSAIDs Therapy and Upper Gastrointestinal Tract – Mechanism of Injury, Mucosal Defense, Risk Factors for Complication Development and Clinical Management

Non steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed medications worldwide because of their analgesic and anti-inflammatory properties. In fact, NSAIDs are generally prescribed for pain management in musculoskeletal or osteoarticolar pathologies and for rheumatic diseases, very common diseases in the general population. About twenty million US patients were prescribed NSAIDs every year. Although NSAIDs are generally well tolerated, chronic therapy is responsible for a significant morbidity and mortality rate; in fact, the incidence of GI events is significantly higher (about four fold) in patients receiving NSAIDs chronic therapy. Adverse gastrointestinal events related to NSAIDs therapy occur in a little but significant amount of patients, resulting in an important morbidity and mortality. In the US more than 150 per 100.000 patients were admitted every year for NSAIDs related adverse events, resulting in about 15000 deaths. The chapter covers the mechanism of NSAIDs related injury, mucosal defense, risk factors for complication development and the clinical management

Lamivudine treatment for severe acute HBV hepatitis

Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision to treat was based on the prolongation of INR together with increasing values of bilirubin and ALT. Four patients received Lamivudine 200 mg/daily until clearance of serum HBV-DNA and then 100 mg/daily until clearance of HBsAg and appearance of anti-HBs antibodies. One patient received 100 mg/daily because of chronic renal impairment. The median period of hospitalization was 13 days, and none of the patients had complications, related either to underlying disease or to therapy. The complete normalization of serum transaminases and bilirubin occurred on average after 5.5 weeks and 3 weeks respectively. All patients cleared serum HBV-DNA within three months, lost HBeAg and HBsAg and seroconverted to anti-HBe; four patients developed anti-HBs at a protective titre. Early antiviral treatment attenuates the clinical and biochemical impairment leading to fast healing and promoting complete recovery

Tumor Location in the Head/Uncinate Process and Presence of Fibrosis Impair the Adequacy of Endoscopic Ultrasound-Guided Tissue Acquisition of Solid Pancreatic Tumors

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) of solid pancreatic tumors shows optimal specificity despite fair sensitivity, with an overall suboptimal diagnostic yield. We aim to quantify the adequacy and accuracy of EUS-TA and assess predictive factors for success, focusing on the presence and degree of specimen fibrosis. All consecutive EUS-TA procedures were retrieved, and the specimens were graded for sample adequacy and fibrosis. The results were evaluated according to patients’ and tumor characteristics and the EUS-TA technique. In total, 407 patients (59% male, 70 [63–77] year old) were included; sample adequacy and diagnostic accuracy were 90.2% and 94.7%, respectively. Fibrosis was significantly more represented in tumors located in the head/uncinate process (p = 0.001). Tumor location in the head/uncinate (OR 0.37 [0.14–0.99]), number of needle passes ≥ 3 (OR 4.53 [2.22–9.28]), and the use of cell block (OR 8.82 [3.23–23.8]) were independently related to adequacy. Severe fibrosis was independently related to false negative results (OR 8.37 [2.33–30.0]). Pancreatic tumors located in the head/uncinate process showed higher fibrosis, resulting in EUS-TA with lower sample adequacy and diagnostic accuracy. We maintain that three or more needle passes and cell block should be done to increase the diagnostic yield

Prospective Evaluation of MGMT-Promoter Methylation Status and Correlations with Outcomes to Temozolomide-Based Chemotherapy in Well-Differentiated Neuroendocrine Tumors

Temozolomide (TEM) as a single agent or in combination with capecitabine (CAPTEM) is active in well-differentiated advanced neuroendocrine tumors (NETs) of gastro-entero-pancreatic and thoracic origin. The predictive role of MGMT-promoter methylation in this setting is controversial. We sought to prospectively evaluate the MGMT-promoter methylation status ability to predict outcomes to TEM-based chemotherapy in patients with NET. A single-center, prospective, observational study has been conducted at the ENETS Center-of-Excellence Outpatient Clinic of the IRCCS Policlinico Sant’Orsola-Malpighi in Bologna, Italy. Patients with advanced, gastro-entero-pancreatic or lung well-differentiated NETs candidate to TEM-based chemotherapy and with available tumor samples for MGMT-promoter methylation assessment were included. The MGMT-promoter methylation status was analyzed by using pyrosequencing. The primary endpoint was progression-free survival (PFS) by the MGMT-promoter methylation status. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival outcomes were compared by restricted mean survival time (RMST) difference. Of 26 screened patients, 22 were finally enrolled in the study. The most frequent NET primary sites were the pancreas (64%) and the lung (23%). MGMT promoter was methylated in five tumors (23%). At a median follow-up time of 47.2 months (95%CI 29.3–89.7), the median PFS was 32.8 months (95%CI 17.2–NA), while the median OS was not reached. Patients in the methylated MGMT group, when compared to those in the unmethylated MGMT group, had longer PFS (median not reached [95%CI NA–NA] vs. 30.2 months [95%CI 15.2–NA], respectively; RMST p = 0.005) and OS (median not reached [95%CI NA–NA] vs. not reached [40.1–NA], respectively; RMST p = 0.019). After adjusting for confounding factors, the MGMT-promoter methylation status was independently associated to the PFS. Numerically higher ORR (60% vs. 24%; p = 0.274) and DCR (100% vs. 88%; p = 1.00) were observed in the methylated vs. unmethylated MGMT group. TEM-based chemotherapy was well-tolerated (adverse events grade ≥3 < 10%). In this prospective study, MGMT-promoter methylation predicted better outcomes to TEM-based chemotherapy in patients with NET

High Doses of Ursodeoxycholic Acid Up-Regulate the Expression of Placental Breast Cancer Resistance Protein in Patients Affected by Intrahepatic Cholestasis of Pregnancy

BACKGROUND: Ursodeoxycholic acid (UDCA) administration in intrahepatic cholestasis of pregnancy (ICP) induces bile acids (BA) efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined. AIM: To determine if placental breast cancer resistance protein (BCRP), able to transport BA, is regulated by UDCA in ICP. METHODS: 32 pregnant women with ICP (14 untreated, 34.9\ub15.17 years; 18 treated with UDCA--25 mg/Kg/day, 32.7\ub14.62 years,) and 12 healthy controls (33.4\ub13.32 years) agreed to participate in the study. Placentas were obtained at delivery and processed for membrane extraction. BCRP protein expression was evaluated by immunoblotting techniques and chemiluminescence quantified with a luminograph measuring emitted photons; mRNA expression with real time PCR. Statistical differences between groups were evaluated by ANOVA with Dunn's Multiple Comparison test. RESULTS: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed among the three groups both for mRNA (ANOVA, p\u200a=\u200a0.0074) and protein (ANOVA, p<0.0001) expression. BCRP expression was similar in controls and in the untreated ICP group. UDCA induced a significant increase in placental BCRP mRNA and protein expression compared to controls (350.7\ub1106.3 vs 100\ub118.68% of controls, p<0.05 and 397.8\ub156.02 vs 100\ub111.44% of controls, p<0.001, respectively) and untreated ICP (90.29\ub117.59% of controls, p<0.05 and 155.0\ub113.87%, p<0.01). CONCLUSION: Our results confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast and show that ICP treatment with high dose UDCA significantly upregulates placental BCRP expression favouring BA efflux from the foetal compartment

Diagnostic performance of endoscopic ultrasound-guided tissue acquisition of splenic lesions: systematic review with pooled analysis

Background: Focal splenic lesions are usually incidentally discovered on radiological assessments. Although percutaneous tissue acquisition (TA) under trans-abdominal ultrasound guidance is a well-established technique for obtaining cyto-histological diagnosis of focal splenic lesions, endoscopic ultrasound (EUS)-guided TA has been described in several studies, reporting different safety and outcomes. The aim was to assess the pooled safety, adequacy, and accuracy of EUS-TA of splenic lesions. Methods: A comprehensive review of available evidence was conducted at the end of November 2021. All studies including more than five patients and reporting about the safety, adequacy, and accuracy of EUS-TA of the spleen were included. Results: Six studies (62 patients) were identified; all studies have been conducted using fine-needle aspiration (FNA) needles. Pooled specimen adequacy and accuracy of EUS-TA for spleen characterization were 92.8% [95% confidence interval (CI), 86.3%-99.3%] and 88.2% (95% CI, 79.3%-97.1%), respectively. The pooled incidence of adverse events (six studies, 62 patients) was 4.7% (95% CI, 0.4%-9.7%). Conclusion: EUS-FNA of the spleen is a safe technique with high diagnostic adequacy and accuracy. The EUS-guided approach could be considered a valid alternative to the percutaneous approach for spleen TA